Calotropis procera: A double edged sword against glioblastoma, inhibiting glioblastoma cell line growth by targeting histone deacetylases (HDAC) and angiogenesis.

Despite substantial investments in anti-glioblastoma (GBM) drug discovery over the last decade, progress is limited to preclinical stages, with clinical studies frequently encountering obstacles. Angiogenic and histone deacetylase inhibitors (HDACi) have shown profound results in pre-clinical studies. Investigating a multicomponent anti-cancer remedy that disrupts the tumor angiogenic blood vessels and simultaneously disrupts HDACs, while inducing minimal side effects, is critically needed. The crude extracts derived from medicinal plants serve as a renewable reservoir of anti-tumor drugs, exhibiting reduced toxicity compared to chemically synthesized formulations. Calotropis procera is a traditional medicinal plant, and its anticancer potential against many cancer cell lines has been reported, however its antiangiogenic and HDAC inhibitory action is largely unknown. The anticancer activity of methanol leaf extract of C. procera was tested in three types of human glioblastoma cell lines. Wild-type and transgenic zebrafish embryos were used to evaluate developmental toxicity and angiogenic activity. A human angiogenic antibody array was used to profile angiogenic proteins in the U251 GM cell line. A real-time reverse transcriptase polymerase chain reaction (RT PCR) assay was used to detect the differential expression of eleven HDAC genes in U251 cells treated with C. procera extract. The extract significantly reduced the proliferation of all three types of GBM cell lines and the cytotoxicity was found to be more pronounced in U251 GM cells, with an IC50 value of 2.63 ± 0.23 µg/ml, possibly by arresting the cell cycle at the G2/M transition. The extract did not exhibit toxic effects in zebrafish embryos, even at concentrations as high as 1000 µg/ml. The extract also inhibited angiogenic blood vessel formation in the transgenic zebrafish model in a dose-dependent manner. The results from the angiogenic antibody array have suggested novel angiogenesis targets that can be utilized to treat GBM. Real-time RT PCR analysis has shown that C. procrea extract caused an upregulation of HDAC5, 7, and 10, while the mRNA of HDAC1, 2, 3 and 8 (Class I HDACs), and HDAC4, 6, and 9 (Class II) were downregulated in U251 GM cells. The cytotoxicity of the C. procera extract on GBM cell lines could be due to its dual action by regulation of both tumor angiogenesis and histone deacetylases enzymes. Through this study, the C. procera leaf extract has been suggested as an effective remedy to treat GBM with minimal toxicity. In addition, various novel angiogenic and HDAC targets has been identified which could be helpful in designing better therapeutic strategies to manage glioblastoma multiforme in human patients.

Assessment of antidiabetic, anti-inflammatory, antioxidant and anticancer activity competence of methonolic extracts of Trianthema ortulacastrum and Andrographis paniculata.

An in-vitro investigation was performed to evaluate and compare the phytochemical, antioxidant, antidiabetic, anti-inflammatory, and anti-lung cancer activities of methanol extracts of aerial parts of Andrographis paniculata and Trianthema portulacastrum. Furthermore studied major functional groups of phytochemicals present in the methanol extracts of these plants through Fourier transform infrared (FTIR) analysis. The results showed that the methanol extract of A. paniculata contain more number of pharmaceutically valuable phytochemicals such as alkaloids, flavonoids, terpenoids, saponin, glycoside, phytosterol, and tannin than T. portulacastrum. Similar way the methanol extract of A. paniculata showed considerable dose dependent antioxidant (DPPH: 63%), antidiabetic (α-amylase: 82.31% and α-glucosidase inhibitions: 72.34%), and anti-inflammatory (albumin-denaturation inhibition: 76.3% and anti-lipoxygenase: 61.2%) activities (at 900 µg mL-1 concentration) than T. portulacastrum. However, the anti-lung cancer activities of these test plants against A549 cells were not considerable. According to FTIR analysis, the A. paniculata methanol extract has a larger number of characteristic peaks attributed to the active functional groups of pharmaceutically valuable bioactive components that belong to different types of phytochemicals. These findings imply that A. paniculata methanol extracts can be used for additional research, such as bioactive compound screening and purification, as well as assessing their potential biomedical uses in various in-vitro and in-research settings.

Interface engineering in ZnO/CdO hybrid nanocomposites to enhanced resistive switching memory for neuromorphic computing.

Resistive random-access memory (RRAMs) has attracted significant interest for their potential applications in embedded storage and neuromorphic computing. Materials based on metal chalcogenides have emerged as promising candidates for the fulfilment of these requirements. Due to its ability to manipulate electronic states and control trap states through controlled compositional dynamics, metal chalcogenide RRAM has excellent non-volatile resistive memory properties. In the present we have synthesized ZnO-CdO hybrid nanocomposite by using hydrothermal method as an active layer. The Ag/C15ZO/Pt hybrid nanocomposite structure memristors showed electrical properties similar to biological synapses. The device exhibited remarkably stable resistive switching properties that have a low SET/RESET (0.41/-0.2) voltage, a high RON/OFF ratio of approximately 105, a high retention stability, excellent endurance reliability up to 104 cycles and multilevel device storage performance by controlling the compliance current. Furthermore, they exhibited an impressive performance in terms of emulating biological synaptic functions, which include long-term potentiation (LTP), long-term depression (LTD), and paired-pulse facilitation (PPF), via the continuous modulation of conductance. The hybrid nanocomposite memristors notably achieved an impressive recognition accuracy of up to 92.6 % for handwritten digit recognition under artificial neural network (ANN). This study shows that hybrid-nanocomposite memristor performance could lead to efficient future neuromorphic architectures.

Phytotoxicity and cytotoxicity attributes of immobilized Bacillus cereus treated and untreated textile effluents on Vigna mungo seeds and Artemia franciscana larvae.

The physicochemical attributes of textile effluents collected from secondary treatment stage was investigated in this study and also assess the biosorption potential of membrane immobilized Bacillus cereus and free form of Bacillus cereus on textile effluent through bioreactor model study to find a sustainable solution to manage the textile effluent as vital need. Furthermore, the phytotoxicity and cytotoxicity nature of treated and untreated textile effluents on Vigna mungo and Artemia franciscana larvae under laboratory conditions as a novel approach. The textile effluent physicochemical parameter analysis results showed that the properties such as colour (Hazen unit), pH, turbidity, As, Biological Oxygen Demand (BOD), Chemical Oxygen Demand (COD), Cd, Cl, Cr, Cu, Hg, Ni, Pb, SO42-, and Zn were beyond the acceptable limits. Bacillus cereus immobilized on a polyethylene membrane eliminated greater amounts of dye (25.0 ± 1.3, 56.5 ± 1.8, 57.18 ± 1.5, and 54.34 ± 1.7 Hazen unit from An1, Ae2, Ve3, and So4 respectively) and pollutants (As: 0.9-2.0, Cd: 6-8, Cr: 300-450, Cu: 5-7, Hg: 0.1-0.7, Ni: 8-14, Pb: 4-5, and Zn: 4-8 mg L-1) from textile effluent in a week of biosorption investigation using a bioreactor model (batch type) compared to a free form of B. cereus on textile effluent. The phytotoxicity and cytotoxicity study results revealed that the membrane immobilized B. cereus treated textile effluent exposure showed reduced phytotoxicity and minimal cytotoxicity (including mortality) percentage compared with free form B. cereus treated and untreated textile effluents. These entire results conclude that the membrane immobilized B. cereus may considerably minimize/detoxify the harmful pollutants from the textile effluents. A large scale level biosorption approach need to be performed to validate the maximum pollutants removing potential of this membrane immobilized bacteria species and optimal conditions for effective remediation.

Causes of higher levels of stress among students in higher education who used eLearning platforms during the COVID-19 pandemic.

Background: This work aims to study the levels of stress among students using e-learning platforms during the COVID-19 pandemic in higher education institutions. The major factors of higher-level stress among the student community focused on this study are: Changes in academic environment, family, social, personal, health and cognitive. Objective: the objective of this research the Partial Least Squares Structural Equation Modelling (PLS-SEM) procedure was used to explore the relationship and its impact on various levels of stress. Results: Data were collected by using a total of 1,000 email IDs of students that were made available by teachers from 12 Indian higher education institutions where they were enrolled and by using a random number method. With this procedure, a total of 800 email IDs were selected. The results drawn from this research are that students experienced more stress due to sudden changes in the academic environment, family, and personal factors. The stress levels of cognitive and social were found to be equally distributed among higher education students, but less than academic environment, family and personal. This research intends to fill the gap of short-term individual psychological changes that occur after the outbreak. Conclusion: Policy-makers can take note of the current study's observations in continuing their fight against COVID-19 pandemic by improving the stability for student risk groups.

Ecogenotoxicological studies for an early toxicity screening and monitoring in Epinephalus chlorostigma and Scamberomorus commerson.

The study was planned to investigate DNA fragmentation in fish to screen aquatic toxicity and in Epinephalus chlorostigma and Scamberomorus commerson collected from Red sea near Jizan, Saudi Arabia from three locations "(Corniche North park: "16.92161, 42.54631; Jizan Port: 16.874, 42.54952" N and Jizan Economic City: 17.26589, 42.34738" ")" were used as a case study for the application of comet assay. The study area of the Red Sea is polluted due to anthropogenic activities and the disposal of wastes from multiple sources. Comet and micronucleus assays were used to detect genotoxicity in these fish species harvested from three sites. The concentration of Pb, Cr, Zn, Mn, Cu, Cd, Sn, and Hg was higher in the water samples collected from the polluted site compared to the non-polluted site of the Red sea. Comet assay for S. commerson showed significant (p < 0.05) genetic damage about 44.33 ± 3.03% DNA in comet tail at site S1. It was subsequently reduced to 31.71 ± 3.52% and 22.11 ± 2.52% at sites S2 and S3. E. chlorostigma also showed significant DNA in comet tail as 17.34 ± 2.19%, 11.87 ± 3.01%, and 36.41 ± 3.98% at site S1-S3, respectively. Significant (p < 0.05) DNA damage was observed in the fishes procured from non-polluted locations and upstream locations. The micronucleus induction in E. chlorostigma was recorded as 23.20 ± 4.19 and 2.20 ± 0.58%, respectively, non-polluted and polluted sites. S. commerson exhibited significant differences between polluted and non-polluted sites (44.80 ± 3.73 and 8.20 ± 2.20‰) polluted and upstream (44.80 ± 3.73 and 20.60 ± 4.02‰), respectively. A significant difference was obtained between E. chlorostigma and S. commerson for nuclear abnormalities S. commerson showed higher frequencies for nuclear deformities than E. chlorostigma. S. commerson showed substantial micronucleus induction frequencies collected from an area of low pollution intensity (upstream). This study showed that E. clorostigma and S. commerson could be successfully used as a bioindicator to determine the health of the Red Sea through the most specific assays such as comet and micronucleus tests as an early warning and to devise the monitoring strategies to ensure a safe supply of fish for human consumption.

Cytotoxicity of Newly Synthesized Quinazoline-Sulfonamide Derivatives in Human Leukemia Cell Lines and Their Effect on Hematopoiesis in Zebrafish Embryos.

Many quinazoline derivatives with pharmacological properties, such as anticancer activity, have been synthesized. Fourteen quinazoline derivatives bearing a substituted sulfonamide moiety (4a-n) were previously synthesized and fully characterized. These compounds exerted antiproliferative activity against cell lines derived from solid tumors. Herein, the antileukemic activities of these compounds (4a-n) against two different leukemia cell lines (Jurkat acute T cell and THP-1 acute monocytic) were investigated. Our investigation included examining their activity in vivo in a zebrafish embryo model. Remarkably, compounds 4a and 4d were the most potent in suppressing cell proliferation, with an IC50 value range of 4-6.5 µM. Flow cytometry analysis indicated that both compounds halted cell progression at the G2/M phase and induced apoptosis in a dose-dependent manner. RT-PCR and Western blot analyses also showed that both compounds effectively induced apoptosis by upregulating the expression of proapoptotic factors while downregulating that of antiapoptotic factors. In vivo animal toxicity assays performed in zebrafish embryos indicated that compound 4d was more toxic than compound 4a, with compound 4d inducing multiple levels of teratogenic phenotypes in zebrafish embryos at a sublethal concentration. Moreover, both compounds perturbed the hematopoiesis process in developing zebrafish embryos. Collectively, our data suggest that compounds 4a and 4d have the potential to be used as antileukemic agents.

Role of silver nanoparticles in fluorimetric determination of urea in urine samples.

Herein, an economical, analytical and sensitive method was established for the fluorometric determination of urea using freshly prepared silver nanoparticles (Ag-NPs) in real urine samples. The standard addition and second-order derivative methods were selected for the ongoing research work to eliminate the possible effect of interferences in a real environment. In this work, Ag-NPs were prepared by reducing silver nitrate salt in the presence of 1,3-di-(1H-imidazole-1-yl) -2-propanol (DIPO) in an aqueous medium. Urea in the urine samples was successfully determined through the complexation of Ag-NPs with urea molecules. The results revealed high percent recovery with ± RSD of urea in the three different urine samples, where percent recoveries by spectrofluorometric standard addition were 99.77 ± 3.4, 100.24 ± 5.1, 100.93 ± 2.8 and that is by the spectrofluorometric second-order derivative method were 103.57 ± 2.4, 101.8 ± 1.3, 98 ± 3.2, respectively. The successful application of these analytical methods in the spectrofluorometric determination of urea in urine samples can accumulate further addition in the effects and possible role of Ag-NPs in the determination of biological molecules in biological and non-biological samples in the scientific as well as clinical fields.

Mutated VWA8 Is Associated With Developmental Delay, Microcephaly, and Scoliosis and Plays a Novel Role in Early Development and Skeletal Morphogenesis in Zebrafish.

Von Willebrand A domain-containing protein 8 (VWA8), also named KIAA0564, is a poorly characterized, mitochondrial matrix-targeted protein having a putative ATPase activity. VWA8 is comprising of ATPase-associated domains and a VWFA domain associated with ATPase activity inside the cell. In the present study, we describe a large consanguineous family of Saudi origin segregating a complex developmental syndrome in an autosomal recessive fashion. All the affected individuals exhibited severe developmental disorders. DNA from three patients was subjected to whole-exome sequencing followed by Sanger sequencing. VWA8 knock-down zebrafish morpholinos were used to study the phenotypic effect of this gene on zebrafish development. A homozygous missense variant [c.947A > G; p.(Asp316Gly)] was identified in exon 8 of the VWA8 gene, which perfectly segregated with the disease phenotype. Using zebrafish morpholino, we observed delayed development at an early stage, lack of movement, light sensitivity, severe skeletal deformity such as scoliosis, and facial dysmorphism. This is the first homozygous variant identified in the VWA8 gene underlying global developmental delay, microcephaly, scoliosis, limbs, and cardiovascular malformations in humans. We provide genetic and molecular evidence using zebrafish morpholino for a homozygous variant in the VWA8 gene, associated with such a complex developmental syndrome in humans.

Tuning of ionic mobility to improve the resistive switching behavior of Zn-doped CeO2.

Correlation between the resistive switching characteristics of Au/Zn-doped CeO2/Au devices and ionic mobility of CeO2 altered by the dopant concentration were explored. It was found that the ionic mobility of CeO2 has a profound effect on the operating voltages of the devices. The magnitude of operating voltage was observed to decrease when the doping concentration of Zn was increased up to 14%. After further increasing the doping level to 24%, the device hardly exhibits any resistive switching. At a low doping concentration, only isolated Vo existed in the CeO2 lattice. At an intermediate doping concentration, the association between dopant and Vo formed (Zn, Vo)× defect clusters. Low number density of these defect clusters initially favored the formation of Vo filament and led to a reduction in operating voltage. As the size and number density of (Zn, Vo)× defect clusters increased at a higher doping concentration, the ionic conductivity was limited with the trapping of isolated Vo by these defect clusters, which resulted in the diminishing of resistive switching. This research work provides a strategy for tuning the mobility of Vo to modulate resistive switching characteristics for non-volatile memory applications.